PROJECT SUMMARY Dental caries are the most prevalent chronic disease worldwide. In fact, in most industrialized countries nearly 100% of the adult population and 60-90% of school-aged children are affected. Detection of non-cavitated lesions which progress slowly enable clinicians to use non-operative preventive strategies to arrest their growth. Moreover, current techniques suffer from high false-positive detection rates. In this proposal, ACIS LLC will develop a novel optical dental imaging technology that utilizes targeted upconversion nanoparticles for noninvasive detection of dental caries and assess its ability to improve the limit of detection (i.e., sensitivity) of dental caries and the specificity (i.e., decrease false positive detection rates) compared to currently marketed technology. Upconversion materials are excited with nonvisible 980 nm light which has deep tissue penetration and emit light in the visible region. This upconversion process greatly reduces background autofluorescence of biological samples resulting in high signal to noise ratios to enhance the sensitivity of detection. This project has two specific aims that : Aim 1: Assess the limit of dental caries detection using a peptide-targeted UCNP that adheres to hydroxyapatite in extracted human tooth specimen; and Aim 2: Assess the limit of dental caries detection of a peptide-targeted UCNP that adheres to S. Mutans in cultured bacteria and extracted tooth specimen with carries. Pending a successful outcome of this Phase I grant application, we will put forward a Phase II grant application involving device development, acute and chronic in vivo toxicity of the UCNPs, and in vivo studies for detection of dental caries in animals pertinent for translation to human trials.